Abstract
Harmine is isolated from the seeds of the medicinal plant, Peganum harmala L., and has been used for thousands of years in the Middle East and China. Harmine has many pharmacological activities including anti-inflammatory, neuroprotective, antidiabetic, and antitumor activities. Moreover, harmine exhibits insecticidal, antiviral, and antibacterial effects. Harmine derivatives exhibit pharmacological effects similar to those of harmine, but with better antitumor activity and low neurotoxicity. Many studies have been conducted on the pharmacological activities of harmine and harmine derivatives. This article reviews the pharmacological effects and associated mechanisms of harmine. In addition, the structure–activity relationship of harmine derivatives has been summarized.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abbassi R, Johns TG, Kassiou M, Munoz L (2015) DYRK1A in neurodegeneration and cancer: molecular basis and clinical implications. Pharmacol Ther 151:87–98. https://doi.org/10.1016/j.pharmthera.2015.03.004
Abelaira HM, Reus GZ, Scaini G, Streck EL, Crippa JA, Quevedo J (2013) beta-Carboline harmine reverses the effects induced by stress on behaviour and citrate synthase activity in the rat prefrontal cortex. Acta Neuropsychiatr 25:328–333. https://doi.org/10.1017/neu.2013.20
Adayev T, Wegiel J, Hwang YW (2011) Harmine is an ATP-competitive inhibitor for dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A). Arch Biochem Biophys 507:212–218. https://doi.org/10.1016/j.abb.2010.12.024
Aguayo-Mazzucato C, Bonner-Weir S (2018) Pancreatic beta cell regeneration as a possible therapy for diabetes. Cell Metab 27:57–67. https://doi.org/10.1016/j.cmet.2017.08.007
Alomar ML, Rasse-Suriani FA, Ganuza A, Coceres VM, Cabrerizo FM, Angel SO (2013) In vitro evaluation of beta-carboline alkaloids as potential anti-toxoplasma agents. BMC Res Notes 6:193–198. https://doi.org/10.1186/1756-0500-6-193
Amoussou NG, Bigot A, Roussakis C, Robert JH (2018) Haspin: a promising target for the design of inhibitors as potent anticancer drugs. Drug Discov Today 23:409–415. https://doi.org/10.1016/j.drudis.2017.10.005
Atteya R, Ashour ME, Ibrahim EE, Farag MA, El-Khamisy SF (2017) Chemical screening identifies the beta-Carboline alkaloid harmine to be synergistically lethal with doxorubicin. Mech Ageing Dev 161:141–148. https://doi.org/10.1016/j.mad.2016.04.012
Balint B, Weber C, Cruzalegui F, Burbridge M, Kotschy A (2017) Structure-based design and synthesis of harmine derivatives with different selectivity profiles in kinase versus monoamine oxidase inhibition. ChemMedChem 12:932–939. https://doi.org/10.1002/cmdc.201600539
Bayih AG, Folefoc A, Mohon AN, Eagon S, Anderson M, Pillai DR (2016) In vitro and in vivo anti-malarial activity of novel harmine-analog heat shock protein 90 inhibitors: a possible partner for artemisinin. Malar J 15:579–589. https://doi.org/10.1186/s12936-016-1625-7
Begum S, Imran Hassan S, Siddiqui BS, Ifzal R, Perwaiz S, Kiran T, Shaheen F, Ghayur MN, Gilani AH (2006) Preparation, structure and spasmolytic activities of some derivatives of harmine series of alkaloids. Nat Prod Res 20:213–227. https://doi.org/10.1080/14786410512331330567
Benzekri R, Bouslama L, Papetti A, Hammami M, Smaoui A, Limam F (2018) Anti HSV-2 activity of Peganum harmala (L.) and isolation of the active compound. Microb Pathog 114:291–298. https://doi.org/10.1016/j.micpath.2017.12.017
Berrougui H, Isabelle M, Cloutier M, Hmamouchi M, Khalil A (2006) Protective effects of Peganum harmala L. extract, harmine and harmaline against human low-density lipoprotein oxidation. J Pharm Pharmacol 58:967–974. https://doi.org/10.1211/jpp.58.7.0012
Boni J, Rubio-Perez C, Lopez-Bigas N, Fillat C, De La Luna S (2020) The DYRK family of kinases in cancer: molecular functions and therapeutic opportunities. Cancers (Basel) 12:2106–2131. https://doi.org/10.3390/cancers12082106
Brierley DI, Davidson C (2013) Harmine augments electrically evoked dopamine efflux in the nucleus accumbens shell. J Psychopharmacol 27:98–108. https://doi.org/10.1177/0269881112463125
Cai CZ, Zhou HF, Yuan NN, Wu MY, Lee SM, Ren JY, Su HX, Lu JJ, Chen XP, Li M, Tan JQ, Lu JH (2019) Natural alkaloid harmine promotes degradation of alpha-synuclein via PKA-mediated ubiquitin-proteasome system activation. Phytomedicine 61:152842–152853. https://doi.org/10.1016/j.phymed.2019.152842
Cao R, Chen H, Peng W, Ma Y, Hou X, Guan H, Liu X, Xu A (2005a) Design, synthesis and in vitro and in vivo antitumor activities of novel beta-carboline derivatives. Eur J Med Chem 40:991–1001. https://doi.org/10.1016/j.ejmech.2005.04.008
Cao R, Peng W, Chen H, Ma Y, Liu X, Hou X, Guan H, Xu A (2005b) DNA binding properties of 9-substituted harmine derivatives. Biochem Biophys Res Commun 338:1557–1563. https://doi.org/10.1016/j.bbrc.2005.10.121
Cao MR, Li Q, Liu ZL, Liu HH, Wang W, Liao XL, Pan YL, Jiang JW (2011) Harmine induces apoptosis in HepG2 cells via mitochondrial signaling pathway. Hepatobiliary Pancreat Dis Int 10:599–604. https://doi.org/10.1016/S1499-3872(11)60102-1
Cao R, Fan W, Guo L, Ma Q, Zhang G, Li J, Chen X, Ren Z, Qiu L (2013) Synthesis and structure-activity relationships of harmine derivatives as potential antitumor agents. Eur J Med Chem 60:135–143. https://doi.org/10.1016/j.ejmech.2012.11.045
Carvalho A, Chu J, Meinguet C, Kiss R, Vandenbussche G, Masereel B, Wouters J, Kornienko A, Pelletier J, Mathieu V (2017) A harmine-derived beta-carboline displays anti-cancer effects in vitro by targeting protein synthesis. Eur J Pharmacol 805:25–35. https://doi.org/10.1016/j.ejphar.2017.03.034
Carvalho A, Viaene J, Vandenbussche G, De Braekeleer K, Masereel B, Wouters J, Souard F, Vander Heyden Y, Van Antwerpen P, Delporte C, Mathieu V (2020) A new potential anti-cancer beta-carboline derivative decreases the expression levels of key proteins involved in glioma aggressiveness: a proteomic investigation. Drug Dev Res 81:32–42. https://doi.org/10.1002/ddr.21600
Chaurasiya ND, Shukla S, Tekwani BL (2017) A combined in vitro assay for evaluation of neurotrophic activity and cytotoxicity. SLAS Discov 22:667–675. https://doi.org/10.1177/2472555217698677
Chen Q, Chao R, Chen H, Hou X, Yan H, Zhou S, Peng W, Xu A (2005) Antitumor and neurotoxic effects of novel harmine derivatives and structure-activity relationship analysis. Int J Cancer 114:675–682. https://doi.org/10.1002/ijc.20703
Chen JY, Lin JR, Tsai FC, Meyer T (2013) Dosage of Dyrk1a shifts cells within a p21-cyclin D1 signaling map to control the decision to enter the cell cycle. Mol Cell 52:87–100. https://doi.org/10.1016/j.molcel.2013.09.009
Chen D, Su A, Fu Y, Wang X, Lv X, Xu W, Xu S, Wang H, Wu Z (2015) Harmine blocks herpes simplex virus infection through downregulating cellular NF-kappaB and MAPK pathways induced by oxidative stress. Antiviral Res 123:27–38. https://doi.org/10.1016/j.antiviral.2015.09.003
Chen C, Cohrs CM, Stertmann J, Bozsak R, Speier S (2017) Human beta cell mass and function in diabetes: recent advances in knowledge and technologies to understand disease pathogenesis. Mol Metab 6:943–957. https://doi.org/10.1016/j.molmet.2017.06.019
Chen D, Tian X, Zou X, Xu S, Wang H, Zheng N, Wu Z (2018) Harmine, a small molecule derived from natural sources, inhibits enterovirus 71 replication by targeting NF-kappaB pathway. Int Immunopharmacol 60:111–120. https://doi.org/10.1016/j.intimp.2018.04.050
Cui G, Shu B, Veeran S, Yuan H, Yi X, Zhong G (2019) Natural beta-carboline alkaloids regulate the PI3K/Akt/mTOR pathway and induce autophagy in insect Sf9 cells. Pestic Biochem Physiol 154:67–77. https://doi.org/10.1016/j.pestbp.2018.12.005
Cui G, Yuan H, Jiang Z, Zhang J, Sun Z, Zhong G (2020) Natural harmine negatively regulates the developmental signaling network of Drosophila melanogaster (Drosophilidae: Diptera) in vivo. Ecotoxicol Environ Saf 190:110134–110142. https://doi.org/10.1016/j.ecoenv.2019.110134
Cuny GD, Ulyanova NP, Patnaik D, Liu JF, Lin X, Auerbach K, Ray SS, **an J, Glicksman MA, Stein RL, Higgins JM (2012) Structure-activity relationship study of beta-carboline derivatives as haspin kinase inhibitors. Bioorg Med Chem Lett 22:2015–2019. https://doi.org/10.1016/j.bmcl.2012.01.028
Dakic V, Maciel RM, Drummond H, Nascimento JM, Trindade P, Rehen SK (2016) Harmine stimulates proliferation of human neural progenitors. PeerJ 4:e2727–e2739. https://doi.org/10.7717/peerj.2727
Ding Y, He J, Huang J, Yu T, Shi X, Zhang T, Yan G, Chen S, Peng C (2019) Harmine induces anticancer activity in breast cancer cells via targeting TAZ. Int J Oncol 54:1995–2004. https://doi.org/10.3892/ijo.2019.4777
Dirice E, Walpita D, Vetere A, Meier BC, Kahraman S, Hu J, Dancik V, Burns SM, Gilbert TJ, Olson DE, Clemons PA, Kulkarni RN, Wagner BK (2016) Inhibition of DYRK1A stimulates human beta-cell proliferation. Diabetes 65:1660–1671. https://doi.org/10.2337/db15-1127
Domonkos C, Zsila F, Fitos I, Visy J, Kassai R, Bálint B, Kotschy A (2015) Synthesis and serum protein binding of novel ring-substituted harmine derivatives. RSC Adv 5:53809–53818. https://doi.org/10.1039/C5RA06426K
Du H, Tian S, Chen J, Gu H, Li N, Wang J (2016) Synthesis and biological evaluation of N(9)-substituted harmine derivatives as potential anticancer agents. Bioorg Med Chem Lett 26:4015–4019. https://doi.org/10.1016/j.bmcl.2016.06.087
Egusa H, Doi M, Saeki M, Fukuyasu S, Akashi Y, Yokota Y, Yatani H, Kamisaki Y (2011) The small molecule harmine regulates NFATc1 and Id2 expression in osteoclast progenitor cells. Bone 49:264–274. https://doi.org/10.1016/j.bone.2011.04.003
El Gendy MA, El-Kadi AO (2013) Harmine and harmaline downregulate TCDD-induced Cyp1a1 in the livers and lungs of C57BL/6 mice. Biomed Res Int 2013:258095–258103. https://doi.org/10.1155/2013/258095
El Gendy MA, Soshilov AA, Denison MS, El-Kadi AO (2012) Transcriptional and posttranslational inhibition of dioxin-mediated induction of CYP1A1 by harmine and harmol. Toxicol Lett 208:51–61. https://doi.org/10.1016/j.toxlet.2011.09.030
Esteban G, Van Schoors J, Sun P, Van Eeckhaut A, Marco-Contelles J, Smolders I, Unzeta M (2017) In-vitro and in-vivo evaluation of the modulatory effects of the multitarget compound ASS234 on the monoaminergic system. J Pharm Pharmacol 69:314–324. https://doi.org/10.1111/jphp.12697
Filali I, Bouajila J, Znati M, Bousejra-El Garah F, Ben Jannet H (2015) Synthesis of new isoxazoline derivatives from harmine and evaluation of their anti-Alzheimer, anti-cancer and anti-inflammatory activities. J Enzyme Inhib Med Chem 30:371–376. https://doi.org/10.3109/14756366.2014.940932
Filali I, Belkacem MA, Ben Nejma A, Souchard JP, Ben Jannet H, Bouajila J (2016a) Synthesis, cytotoxic, anti-lipoxygenase and anti-acetylcholinesterase capacities of novel derivatives from harmine. J Enzyme Inhib Med Chem 31:23–33. https://doi.org/10.3109/14756366.2016.1163342
Filali I, Romdhane A, Znati M, Jannet HB, Bouajila J (2016b) Synthesis of new harmine isoxazoles and evaluation of their potential anti-alzheimer, anti-inflammatory, and anticancer activities. Med Chem 12:184–190. https://doi.org/10.2174/1573406411666150911115850
Fortunato JJ, Reus GZ, Kirsch TR, Stringari RB, Stertz L, Kapczinski F, Pinto JP, Hallak JE, Zuardi AW, Crippa JA, Quevedo J (2009) Acute harmine administration induces antidepressive-like effects and increases BDNF levels in the rat hippocampus. Prog Neuropsychopharmacol Biol Psychiatry 33:1425–1430. https://doi.org/10.1016/j.pnpbp.2009.07.021
Fortunato JJ, Reus GZ, Kirsch TR, Stringari RB, Fries GR, Kapczinski F, Hallak JE, Zuardi AW, Crippa JA, Quevedo J (2010a) Chronic administration of harmine elicits antidepressant-like effects and increases BDNF levels in rat hippocampus. J Neural Transm (Vienna) 117:1131–1137. https://doi.org/10.1007/s00702-010-0451-2
Fortunato JJ, Reus GZ, Kirsch TR, Stringari RB, Fries GR, Kapczinski F, Hallak JE, Zuardi AW, Crippa JA, Quevedo J (2010b) Effects of beta-carboline harmine on behavioral and physiological parameters observed in the chronic mild stress model: further evidence of antidepressant properties. Brain Res Bull 81:491–496. https://doi.org/10.1016/j.brainresbull.2009.09.008
Frederick R, Bruyere C, Vancraeynest C, Reniers J, Meinguet C, Pochet L, Backlund A, Masereel B, Kiss R, Wouters J (2012) Novel trisubstituted harmine derivatives with original in vitro anticancer activity. J Med Chem 55:6489–6501. https://doi.org/10.1021/jm300542e
Frost D, Meechoovet B, Wang T, Gately S, Giorgetti M, Shcherbakova I, Dunckley T (2011) beta-carboline compounds, including harmine, inhibit DYRK1A and tau phosphorylation at multiple Alzheimer’s disease-related sites. PLoS ONE 6:e19264–e19272. https://doi.org/10.1371/journal.pone.0019264
Fujiwara N, Lee JW, Kumakami-Sakano M, Otsu K, Woo JT, Iseki S, Ota MS (2018) Harmine promotes molar root development via SMAD1/5/8 phosphorylation. Biochem Biophys Res Commun 497:924–929. https://doi.org/10.1016/j.bbrc.2017.12.062
Gao J, Zhu H, Wan H, Zou X, Ma X, Gao G (2017) Harmine suppresses the proliferation and migration of human ovarian cancer cells through inhibiting ERK/CREB pathway. Oncol Rep 38:2927–2934. https://doi.org/10.3892/or.2017.5952
Geng X, Ren Y, Wang F, Tian D, Yao X, Zhang Y, Tang J (2018) Harmines inhibit cancer cell growth through coordinated activation of apoptosis and inhibition of autophagy. Biochem Biophys Res Commun 498:99–104. https://doi.org/10.1016/j.bbrc.2018.02.205
Ghosh T, Sarkar S, Bhattacharjee P, Jana GC, Hossain M, Pandya P, Bhadra K (2020) In vitro relationship between serum protein binding to beta-carboline alkaloids: a comparative cytotoxic, spectroscopic and calorimetric assays. J Biomol Struct Dyn 38:1103–1118. https://doi.org/10.1080/07391102.2019.1595727
Giacobbo BL, Doorduin J, Moraga-Amaro R, Nazario LR, Schildt A, Bromberg E, Dierckx R, De Vries EFJ (2020) Chronic harmine treatment has a delayed effect on mobility in control and socially defeated rats. Psychopharmacology 237:1595–1606. https://doi.org/10.1007/s00213-020-05483-2
Gockler N, Jofre G, Papadopoulos C, Soppa U, Tejedor FJ, Becker W (2009) Harmine specifically inhibits protein kinase DYRK1A and interferes with neurite formation. FEBS J 276:6324–6337. https://doi.org/10.1111/j.1742-4658.2009.07346.x
Guan Y, Louis ED, Zheng W (2001) Toxicokinetics of tremorogenic natural products, harmane and harmine, in male Sprague-Dawley rats. J Toxicol Environ Health A 64:645–660. https://doi.org/10.1080/152873901753246241
Guo L, Cao R, Fan W, Ma Q (2014) Synthesis and biological evaluation of 1, 2, 7, 9-tetrasubstituted harmine derivatives as potential antitumor agents. Chem J Chinese Univ 35:518–523. https://doi.org/10.7503/cjcu20130683
Guo L, Cao R, Fan W, Gan Z, Ma Q (2016) Design, synthesis and in vitro antitumor activities of novel bivalent β-carbolines. Chem J Chin Univ 37:1093–1099. https://doi.org/10.7503/cjcu20160103
Guo L, Ma Q, Chen W, Fan W, Zhang J, Dai B (2019) Synthesis and biological evaluation of novel N(9)-heterobivalent beta-carbolines as angiogenesis inhibitors. J Enzyme Inhib Med Chem 34:375–387. https://doi.org/10.1080/14756366.2018.1497619
Hai-Rong C, **ang H, **ao-Rong Z (2019) Harmine suppresses bladder tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis. Biosci Rep 39:BSR20190155–BSR20190164. https://doi.org/10.1042/BSR20190155
Haider S, Alhusban M, Chaurasiya ND, Tekwani BL, Chittiboyina AG, Khan IA (2018) Isoform selectivity of harmine-conjugated 1,2,3-triazoles against human monoamine oxidase. Future Med Chem 10:1435–1448. https://doi.org/10.4155/fmc-2018-0006
Hamsa TP, Kuttan G (2010) Harmine inhibits tumour specific neo-vessel formation by regulating VEGF, MMP, TIMP and pro-inflammatory mediators both in vivo and in vitro. Eur J Pharmacol 649:64–73. https://doi.org/10.1016/j.ejphar.2010.09.010
Hamsa T, Kuttan G (2011a) Studies on anti-metastatic and anti-invasive effects of harmine using highly metastatic murine B16F–10 melanoma cells. J Environ Pathol Toxicol Oncol 30:123–137. https://doi.org/10.1615/JEnvironPatholToxicolOncol.v30.i2.40
Hamsa TP, Kuttan G (2011b) Harmine activates intrinsic and extrinsic pathways of apoptosis in B16F–10 melanoma. Chin Med 6:11–18. https://doi.org/10.1186/1749-8546-6-11
Hara ES, Ono M, Kubota S, Sonoyama W, Oida Y, Hattori T, Nishida T, Furumatsu T, Ozaki T, Takigawa M, Kuboki T (2013) Novel chondrogenic and chondroprotective effects of the natural compound harmine. Biochimie 95:374–381. https://doi.org/10.1016/j.biochi.2012.10.016
He D, Wu H, Wei Y, Liu W, Huang F, Shi H, Zhang B, Wu X, Wang C (2015a) Effects of harmine, an acetylcholinesterase inhibitor, on spatial learning and memory of APP/PS1 transgenic mice and scopolamine-induced memory impairment mice. Eur J Pharmacol 768:96–107. https://doi.org/10.1016/j.ejphar.2015.10.037
He J, Yao J, Sheng H, Zhu J (2015b) Involvement of the dual-specificity tyrosine phosphorylation-regulated kinase 1A-alternative splicing factor-calcium/calmodulin-dependent protein kinase IIdelta signaling pathway in myocardial infarction-induced heart failure of rats. J Card Fail 21:751–760. https://doi.org/10.1016/j.cardfail.2015.05.015
Huang J, Yin H, Rao SS, **e PL, Cao X, Rao T, Liu SY, Wang ZX, Cao J, Hu Y, Zhang Y, Luo J, Tan YJ, Liu ZZ, Wu B, Hu XK, Chen TH, Chen CY, **e H (2018) Harmine enhances type H vessel formation and prevents bone loss in ovariectomized mice. Theranostics 8:2435–2446. https://doi.org/10.7150/thno.22144
Hutterer C, Milbradt J, Hamilton S, Zaja M, Leban J, Henry C, Vitt D, Steingruber M, Sonntag E, Zeittrager I, Bahsi H, Stamminger T, Rawlinson W, Strobl S, Marschall M (2017) Inhibitors of dual-specificity tyrosine phosphorylation-regulated kinases (DYRK) exert a strong anti-herpesviral activity. Antiviral Res 143:113–121. https://doi.org/10.1016/j.antiviral.2017.04.003
Im JH, ** YR, Lee JJ, Yu JY, Han XH, Im SH, Hong JT, Yoo HS, Pyo MY, Yun YP (2009) Antiplatelet activity of beta-carboline alkaloids from Perganum harmala: a possible mechanism through inhibiting PLCgamma2 phosphorylation. Vascul Pharmacol 50:147–152. https://doi.org/10.1016/j.vph.2008.11.008
Jain S, Panuganti V, Jha S, Roy I (2020) Harmine acts as an indirect inhibitor of intracellular protein aggregation. ACS Omega 5:5620–5628. https://doi.org/10.1021/acsomega.9b02375
Jiang B, Meng L, Zou N, Wang H, Li S, Huang L, Cheng X, Wang Z, Chen W, Wang C (2019) Mechanism-based pharmacokinetics-pharmacodynamics studies of harmine and harmaline on neurotransmitters regulatory effects in healthy rats: challenge on monoamine oxidase and acetylcholinesterase inhibition. Phytomedicine 62:152967–152981. https://doi.org/10.1016/j.phymed.2019.152967
Jimenez J, Riveron-Negrete L, Abdullaev F, Espinosa-Aguirre J, Rodriguez-Arnaiz R (2008) Cytotoxicity of the beta-carboline alkaloids harmine and harmaline in human cell assays in vitro. Exp Toxicol Pathol 60:381–389. https://doi.org/10.1016/j.etp.2007.12.003
Kondoh D, Yamamoto S, Tomita T, Miyazaki K, Itoh N, Yasumoto Y, Oike H, Doi R, Oishi K (2014) Harmine lengthens circadian period of the mammalian molecular clock in the suprachiasmatic nucleus. Biol Pharm Bull 37:1422–1427. https://doi.org/10.1248/bpb.b14-00229
Kruitwagen HS, Westendorp B, Viebahn CS, Post K, Van Wolferen ME, Oosterhoff LA, Egan DA, Delabar JM, Toussaint MJ, Schotanus BA, De Bruin A, Rothuizen J, Penning LC, Spee B (2018) DYRK1A Is a regulator of S-phase entry in hepatic progenitor cells. Stem Cells Dev 27:133–146. https://doi.org/10.1089/scd.2017.0139
Kumar K, Wang P, Sanchez R, Swartz EA, Stewart AF, Devita RJ (2018) Development of kinase-selective, harmine-based DYRK1A inhibitors that induce pancreatic human beta-cell proliferation. J Med Chem 61:7687–7699. https://doi.org/10.1021/acs.jmedchem.8b00658
Kumar K, Wang P, Ethan AS, Khamrui S, Secor C, Michael BL, Sanchez R, Andrew FS, Devita RJ (2020a) Structure-activity relationships and biological evaluation of 7-substituted harmine analogs for human beta-cell proliferation. Molecules 25:1983–2000. https://doi.org/10.3390/molecules25081983
Kumar K, Wang P, Wilson J, Zlatanic V, Berrouet C, Khamrui S, Secor C, Swartz EA, Lazarus M, Sanchez R, Stewart AF, Garcia-Ocana A, Devita RJ (2020b) Synthesis and biological validation of a harmine-based, central nervous system (CNS)-avoidant, selective, human beta-cell regenerative dual-specificity tyrosine phosphorylation-regulated kinase A (DYRK1A) inhibitor. J Med Chem 63:2986–3003. https://doi.org/10.1021/acs.jmedchem.9b01379
Le Moigne R, Subra F, Karam M, Auclair C (2020) The beta-carboline harmine induces actin dynamic remodeling and abrogates the malignant phenotype in tumorigenic cells. Cells 9:1168–1185. https://doi.org/10.3390/cells9051168
Li Y, Sattler R, Yang EJ, Nunes A, Ayukawa Y, Akhtar S, Ji G, Zhang PW, Rothstein JD (2011) Harmine, a natural beta-carboline alkaloid, upregulates astroglial glutamate transporter expression. Neuropharmacology 60:1168–1175. https://doi.org/10.1016/j.neuropharm.2010.10.016
Li S, Wang A, Gu F, Wang Z, Tian C, Qian Z, Tang L, Gu Y (2015) Novel harmine derivatives for tumor targeted therapy. Oncotarget 6:8988–9001. https://doi.org/10.18632/oncotarget.3276
Li C, Wang Y, Wang C, Yi X, Li M, He X (2017a) Anticancer activities of harmine by inducing a pro-death autophagy and apoptosis in human gastric cancer cells. Phytomedicine 28:10–18. https://doi.org/10.1016/j.phymed.2017.02.008
Li S, Teng L, Liu W, Cheng X, Jiang B, Wang Z, Wang C (2017b) Interspecies metabolic diversity of harmaline and harmine in in vitro 11 mammalian liver microsomes. Drug Test Anal 9:754–768. https://doi.org/10.1002/dta.2028
Li S, Zhang Y, Deng G, Wang Y, Qi S, Cheng X, Ma Y, **e Y, Wang C (2017c) Exposure characteristics of the analogous beta-carboline alkaloids harmaline and harmine based on the efflux transporter of multidrug resistance protein 2. Front Pharmacol 8:541–548. https://doi.org/10.3389/fphar.2017.00541
Li SP, Wang YW, Qi SL, Zhang YP, Deng G, Ding WZ, Ma C, Lin QY, Guan HD, Liu W, Cheng XM, Wang CH (2018) Analogous beta-carboline alkaloids harmaline and harmine ameliorate scopolamine-induced cognition dysfunction by attenuating acetylcholinesterase activity, oxidative stress, and inflammation in mice. Front Pharmacol 9:346–361. https://doi.org/10.3389/fphar.2018.00346
Li X, Wu X, Gao Y, Hao L (2019a) Synergistic effects and mechanisms of combined treatment with harmine hydrochloride and azoles for resistant Candida albicans. Front Microbiol 10:2295–2306. https://doi.org/10.3389/fmicb.2019.02295
Li YL, Ding K, Hu X, Wu LW, Zhou DM, Rao MJ, Lin NM, Zhang C (2019b) DYRK1A inhibition suppresses STAT3/EGFR/Met signalling and sensitizes EGFR wild-type NSCLC cells to AZD9291. J Cell Mol Med 23:7427–7437. https://doi.org/10.1111/jcmm.14609
Li Y, Zhou D, Xu S, Rao M, Zhang Z, Wu L, Zhang C, Lin N (2020) DYRK1A suppression restrains Mcl-1 expression and sensitizes NSCLC cells to Bcl-2 inhibitors. Cancer Biol Med 17:387–400. https://doi.org/10.20892/j.issn.2095-3941.2019.0380
Lim HC, Cha BY, Song SU, Yun JH (2018) Harmine promotes periodontal ligament cell-induced tissue regeneration. Oral Dis 24:456–464. https://doi.org/10.1111/odi.12770
Liu H, Han D, Liu Y, Hou X, Wu J, Li H, Yang J, Shen C, Yang G, Fu C, Li X, Che H, Ai J, Zhao S (2013) Harmine hydrochloride inhibits Akt phosphorylation and depletes the pool of cancer stem-like cells of glioblastoma. J Neurooncol 112:39–48. https://doi.org/10.1007/s11060-012-1034-x
Liu J, Li Q, Liu Z, Lin L, Zhang X, Cao M, Jiang J (2016) Harmine induces cell cycle arrest and mitochondrial pathway-mediated cellular apoptosis in SW620 cells via inhibition of the Akt and ERK signaling pathways. Oncol Rep 35:3363–3370. https://doi.org/10.3892/or.2016.4695
Liu F, Wu J, Gong Y, Wang P, Zhu L, Tong L, Chen X, Ling Y, Huang C (2017a) Harmine produces antidepressant-like effects via restoration of astrocytic functions. Prog Neuropsychopharmacol Biol Psychiatry 79:258–267. https://doi.org/10.1016/j.pnpbp.2017.06.012
Liu X, Li M, Tan S, Wang C, Fan S, Huang C (2017b) Harmine is an inflammatory inhibitor through the suppression of NF-kappaB signaling. Biochem Biophys Res Commun 489:332–338. https://doi.org/10.1016/j.bbrc.2017.05.126
Liu WZ, Huang BW, You WJ, Hu P, Wang XH, Zhang JY, Xu XB, Zhang ZY, Pan BX, Zhang WH (2018) Harmine enhances GABAergic transmission onto basoamygdala projection neurons in mice. Brain Res Bull 137:294–300. https://doi.org/10.1016/j.brainresbull.2018.01.004
Liu P, Li H, Wang Y, Su X, Li Y, Yan M, Ma L, Che H (2020) Harmine ameliorates cognitive impairment by inhibiting NLRP3 Inflammasome Activation And Enhancing the BDNF/TrkB signaling pathway in STZ-induced diabetic rats. Front Pharmacol 11:535–543. https://doi.org/10.3389/fphar.2020.00535
Ma Y, Wink M (2010) The beta-carboline alkaloid harmine inhibits BCRP and can reverse resistance to the anticancer drugs mitoxantrone and camptothecin in breast cancer cells. Phytother Res 24:146–149. https://doi.org/10.1002/ptr.2860
Ma Q, Chen W, Chen W (2016) Anti-tumor angiogenesis effect of a new compound: B-9-3 through interference with VEGFR2 signaling. Tumour Biol 37:6107–6116. https://doi.org/10.1007/s13277-015-4473-0
Marx S, Bodart L, Tumanov N, Wouters J (2019) Design and synthesis of a new soluble natural beta-carboline derivative for preclinical study by intravenous injection. Int J Mol Sci 20:1491–1505. https://doi.org/10.3390/ijms20061491
Meinguet C, Bruyere C, Frederick R, Mathieu V, Vancraeynest C, Pochet L, Laloy J, Mortier J, Wolber G, Kiss R, Masereel B, Wouters J (2015) 3D-QSAR, design, synthesis and characterization of trisubstituted harmine derivatives with in vitro antiproliferative properties. Eur J Med Chem 94:45–55. https://doi.org/10.1016/j.ejmech.2015.02.044
Mennenga SE, Gerson JE, Dunckley T, Bimonte-Nelson HA (2015) Harmine treatment enhances short-term memory in old rats: dissociation of cognition and the ability to perform the procedural requirements of maze testing. Physiol Behav 138:260–265. https://doi.org/10.1016/j.physbeh.2014.09.001
Miao JF, Peng YF, Chen S, Gao WJ, Yang QX, Zhu P, Guo J, Tao J, Luo L, Zhang Y, Ling Y (2018) A novel harmine derivative, N-(4-(hydroxycarbamoyl)benzyl)-1-(4- methoxyphenyl)-9H-pyrido[3,4-b]indole-3-carboxamide (HBC), as histone deacetylase inhibitor: in vitro antiproliferation, apoptosis induction, cell cycle arrest, and antimetastatic effects. Eur J Pharmacol 824:78–88. https://doi.org/10.1016/j.ejphar.2018.02.004
Miller MJ, Albarracin-Jordan J, Moore C, Capriles JM (2019) Chemical evidence for the use of multiple psychotropic plants in a 1,000-year-old ritual bundle from South America. Proc Natl Acad Sci USA 116:11207–11212. https://doi.org/10.1073/pnas.1902174116
Moura DJ, Richter MF, Boeira JM, Pegas Henriques JA, Saffi J (2007) Antioxidant properties of beta-carboline alkaloids are related to their antimutagenic and antigenotoxic activities. Mutagenesis 22:293–302. https://doi.org/10.1093/mutage/gem016
Mukusheva G, Nurmaganbetov Z, Ismagulova N, Ponamareva O, Burdelnaya E, Turmukhambetov A, Kazantsev A, Adekenov S (2011) Synthesis and phagocytosis-stimulating activity of harmine and glaucine N-oxides. Pharm Chem J 45:458–460. https://doi.org/10.1007/s11094-011-0654-3
Nafisi S, Bonsaii M, Maali P, Khalilzadeh MA, Manouchehri F (2010) Beta-carboline alkaloids bind DNA. J Photochem Photobiol B 100:84–91. https://doi.org/10.1016/j.jphotobiol.2010.05.005
Nafisi S, Panahyab A, Bagheri Sadeghi G (2012) Interactions between β-carboline alkaloids and bovine serum albumin: investigation by spectroscopic approach. J Lumin 132:2361–2366. https://doi.org/10.1016/j.jlumin.2012.03.075
Nenaah G (2010) Antibacterial and antifungal activities of (beta)-carboline alkaloids of Peganum harmala (L) seeds and their combination effects. Fitoterapia 81:779–782. https://doi.org/10.1016/j.fitote.2010.04.004
Nie T, Hui X, Mao L, Nie B, Li K, Sun W, Gao X, Tang X, Xu Y, Jiang B, Tu Z, Li P, Ding K, Han W, Zhang S, Xu A, Ding S, Liu P, Patterson A, Cooper G, Wu D (2016) Harmine induces adipocyte thermogenesis through RAC1-MEK-ERK-CHD4 axis. Sci Rep 6:36382–36391. https://doi.org/10.1038/srep36382
Niu X, Yao Q, Li W, Zang L, Li W, Zhao J, Liu F, Zhi W (2019) Harmine mitigates LPS-induced acute kidney injury through inhibition of the TLR4-NF-kappaB/NLRP3 inflammasome signalling pathway in mice. Eur J Pharmacol 849:160–169. https://doi.org/10.1016/j.ejphar.2019.01.062
Onishi Y, Oishi K, Kawano Y, Yamazaki Y (2012) The harmala alkaloid harmine is a modulator of circadian Bmal1 transcription. Biosci Rep 32:45–52. https://doi.org/10.1042/BSR20110002
Oodi A, Norouzi H, Amirizadeh N, Nikougoftar M, Vafaie Z (2017) Harmine, a novel DNA methyltransferase 1 inhibitor in the leukemia cell line. Indian J Hematol Blood Transfus 33:509–515. https://doi.org/10.1007/s12288-016-0770-z
Owaisat S, Raffa RB, Rawls SM (2012) In vivo comparison of harmine efficacy against psychostimulants: preferential inhibition of the cocaine response through a glutamatergic mechanism. Neurosci Lett 525:12–16. https://doi.org/10.1016/j.neulet.2012.07.052
Pagano B, Caterino M, Filosa R, Giancola C (2017) Binding of harmine derivatives to DNA: a spectroscopic investigation. Molecules 22:1831–1838. https://doi.org/10.3390/molecules22111831
Park J, Song WJ, Chung KC (2009) Function and regulation of Dyrk1A: towards understanding down syndrome. Cell Mol Life Sci 66:3235–3240. https://doi.org/10.1007/s00018-009-0123-2
Perez Martin JM, Labrador V, Fernandez Freire P, Molero ML, Hazen MJ (2004) Ultrastructural changes induced in HeLa cells after phototoxic treatment with harmine. J Appl Toxicol 24:197–201. https://doi.org/10.1002/jat.972
Perković I, Raić-Malić S, Fontinha D, Prudêncio M, Pessanha L, Held J, Tandarić T, Vianello R, Zorc B, Rajic Z (2020) Harmicines—harmine and cinnamic acid hybrids as novel antiplasmodial hits. Eur J Med Chem 187:111927–111942. https://doi.org/10.1016/j.ejmech.2019.111927
Pierson E, Haufroid M, Gosain TP, Chopra P, Singh R, Wouters J (2020) Identification and repurposing of trisubstituted harmine derivatives as novel inhibitors of mycobacterium tuberculosis phosphoserine phosphatase. Molecules 25:415–431. https://doi.org/10.3390/molecules25020415
Quintana VM, Piccini LE, Panozzo Zenere JD, Damonte EB, Ponce MA, Castilla V (2016) Antiviral activity of natural and synthetic beta-carbolines against dengue virus. Antiviral Res 134:26–33. https://doi.org/10.1016/j.antiviral.2016.08.018
Reniers J, Robert S, Frederick R, Masereel B, Vincent S, Wouters J (2011) Synthesis and evaluation of beta-carboline derivatives as potential monoamine oxidase inhibitors. Bioorg Med Chem 19:134–144. https://doi.org/10.1016/j.bmc.2010.11.041
Reus GZ, Stringari RB, De Souza B, Petronilho F, Dal-Pizzol F, Hallak JE, Zuardi AW, Crippa JA, Quevedo J (2010) Harmine and imipramine promote antioxidant activities in prefrontal cortex and hippocampus. Oxid Med Cell Longev 3:325–331. https://doi.org/10.4161/oxim.3.5.13109
Ruan S, Jia F, Li J (2017) Potential antitumor effect of harmine in the treatment of thyroid cancer. Evid Based Complement Alternat Med 2017:9402615–9402621. https://doi.org/10.1155/2017/9402615
Ruben K, Wurzlbauer A, Walte A, Sippl W, Bracher F, Becker W (2015) Selectivity profiling and biological activity of novel beta-carbolines as potent and selective DYRK1 kinase inhibitors. PLoS ONE 10:e0132453–e0132470. https://doi.org/10.1371/journal.pone.0132453
Salahshoor MR, Mahmoudian ZG, Roshankhah S, Farokhi M, Jalili C (2019a) Harmine shows therapeutic activity on nicotine-induced liver failure in mice. Histol Histopathol 18122:1185–1193. https://doi.org/10.14670/HH-18-122
Salahshoor MR, Roshankhah S, Motavalian V, Jalili C (2019b) Effect of harmine on nicotine-induced kidney dysfunction in male mice. Int J Prev Med 10:97–103. https://doi.org/10.4103/ijpvm.IJPVM_85_18
Seifert A, Allan LA, Clarke PR (2008) DYRK1A phosphorylates caspase 9 at an inhibitory site and is potently inhibited in human cells by harmine. FEBS J 275:6268–6280. https://doi.org/10.1111/j.1742-4658.2008.06751.x
Shahinas D, Macmullin G, Benedict C, Crandall I, Pillai DR (2012) Harmine is a potent antimalarial targeting Hsp90 and synergizes with chloroquine and artemisinin. Antimicrob Agents Chemother 56:4207–4213. https://doi.org/10.1128/AAC.00328-12
Sharma S, Yadav M, Gupta SP, Pandav K, Kumar S (2016) Spectroscopic and structural studies on the interaction of an anticancer beta-carboline alkaloid, harmine with GC and AT specific DNA oligonucleotides. Chem Biol Interact 260:256–262. https://doi.org/10.1016/j.cbi.2016.08.025
Shen J, Song G, An M, Li X, Wu N, Ruan K, Hu J, Hu R (2014) The use of hollow mesoporous silica nanospheres to encapsulate bortezomib and improve efficacy for non-small cell lung cancer therapy. Biomaterials 35:316–326. https://doi.org/10.1016/j.biomaterials.2013.09.098
Shen J, Wang B, Zhang T, Zhu N, Wang Z, ** J, He Y, Hu M (2018) Suppression of non-small cell lung cancer growth and metastasis by a novel small molecular activator of RECK. Cell Physiol Biochem 45:1807–1817. https://doi.org/10.1159/000487872
Shi CC, Liao JF, Chen CF (2001) Comparative study on the vasorelaxant effects of three harmala alkaloids in vitro. Jpn J Pharmacol 85:299–305. https://doi.org/10.1254/jjp.85.299
Shi XY, Liu W, Zhang L, Li SP, Cheng XM, ** Y, Wang CH (2014) Pharmacokinetics of harmaline, harmine and their metabolites in rats administered with total alkaloid extracts from Peganum harmala L. Chin Tradit Pat Med 36:1169–1775. https://doi.org/10.3969/j.issn.1001-1528.2014.06.013
Shu B, Zhang J, Jiang Z, Cui G, Veeran S, Zhong G (2019) Harmine induced apoptosis in Spodoptera frugiperda Sf9 cells by activating the endogenous apoptotic pathways and inhibiting DNA topoisomerase I activity. Pestic Biochem Physiol 155:26–35. https://doi.org/10.1016/j.pestbp.2019.01.002
Song Y, Kesuma D, Wang J, Deng Y, Duan J, Wang JH, Qi RZ (2004) Specific inhibition of cyclin-dependent kinases and cell proliferation by harmine. Biochem Biophys Res Commun 317:128–132. https://doi.org/10.1016/j.bbrc.2004.03.019
Sun P, Zhang S, Li Y, Wang L (2014) Harmine mediated neuroprotection via evaluation of glutamate transporter 1 in a rat model of global cerebral ischemia. Neurosci Lett 583:32–36. https://doi.org/10.1016/j.neulet.2014.09.023
Sun K, Tang XH, **e YK (2015) Paclitaxel combined with harmine inhibits the migration and invasion of gastric cancer cells through downregulation of cyclooxygenase-2 expression. Oncol Lett 10:1649–1654. https://doi.org/10.3892/ol.2015.3425
Tabari MA, Youssefi MR, Moghadamnia AA (2017) Antitrichomonal activity of Peganum harmala alkaloid extract against trichomoniasis in pigeon (Columba livia domestica). Br Poult Sci 58:236–241. https://doi.org/10.1080/00071668.2017.1280725
Uhl KL, Schultz CR, Geerts D, Bachmann AS (2018) Harmine, a dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) inhibitor induces caspase-mediated apoptosis in neuroblastoma. Cancer Cell Int 18:82–95. https://doi.org/10.1186/s12935-018-0574-3
Vignoni M, Erra-Balsells R, Epe B, Cabrerizo FM (2014) Intra- and extra-cellular DNA damage by harmine and 9-methyl-harmine. J Photochem Photobiol B 132:66–71. https://doi.org/10.1016/j.jphotobiol.2014.01.020
Waki H, Park KW, Mitro N, Pei L, Damoiseaux R, Wilpitz DC, Reue K, Saez E, Tontonoz P (2007) The small molecule harmine is an antidiabetic cell-type-specific regulator of PPARgamma expression. Cell Metab 5:357–370. https://doi.org/10.1016/j.cmet.2007.03.010
Wang P, Alvarez-Perez JC, Felsenfeld DP, Liu H, Sivendran S, Bender A, Kumar A, Sanchez R, Scott DK, Garcia-Ocana A, Stewart AF (2015) A high-throughput chemical screen reveals that harmine-mediated inhibition of DYRK1A increases human pancreatic beta cell replication. Nat Med 21:383–388. https://doi.org/10.1038/nm.3820
Wu LW, Zhang JK, Rao M, Zhang ZY, Zhu HJ, Zhang C (2019) Harmine suppresses the proliferation of pancreatic cancer cells and sensitizes pancreatic cancer to gemcitabine treatment. Onco Targets Ther 12:4585–4593. https://doi.org/10.2147/OTT.S205097
**a Y, Qi Y-M, Yu X-H, Wang B-F, Cao R-H, Jiang D (2018) Nematicidal effect against Bursaphelenchus xylophilus of harmine quaternary ammonium derivatives, inhibitory activity and molecular docking studies on acetylcholinesterase. Eur J Plant Pathol 153:239–250. https://doi.org/10.1007/s10658-018-1559-8
Yamazaki Y, Kawano Y (2011) Inhibitory effects of herbal alkaloids on the tumor necrosis factor-alpha and nitric oxide production in lipopolysaccharide-stimulated RAW264 macrophages. Chem Pharm Bull (Tokyo) 59:388–391. https://doi.org/10.1248/cpb.59.388
Yang X, Wang W, Qin JJ, Wang MH, Sharma H, Buolamwini JK, Wang H, Zhang R (2012) JKA97, a novel benzylidene analog of harmine, exerts anti-cancer effects by inducing G1 arrest, apoptosis, and p53-independent up-regulation of p21. PLoS ONE 7:e34303–e34310. https://doi.org/10.1371/journal.pone.0034303
Yanuk JG, Denofrio MP, FaO R-S, Villarruel FD, Fassetta F, Garcia Einschlag FS, Erra-Balsells R, Epe B, Cabrerizo FM (2018) DNA damage photo-induced by chloroharmine isomers: hydrolysis versus oxidation of nucleobases. Org Biomol Chem 16:2170–2184. https://doi.org/10.1039/c8ob00162f
Yochum ZA, Cades J, Mazzacurati L, Neumann NM, Khetarpal SK, Chatterjee S, Wang H, Attar MA, Huang EH, Chatley SN, Nugent K, Somasundaram A, Engh JA, Ewald AJ, Cho YJ, Rudin CM, Tran PT, Burns TF (2017) A First-in-class twist1 inhibitor with activity in oncogene-driven lung cancer. Mol Cancer Res 15:1764–1776. https://doi.org/10.1158/1541-7786.MCR-17-0298
Yochum ZA, Cades J, Wang H, Chatterjee S, Simons BW, O’brien JP, Khetarpal SK, Lemtiri-Chlieh G, Myers KV, Huang EH, Rudin CM, Tran PT, Burns TF (2019) Targeting the EMT transcription factor TWIST1 overcomes resistance to EGFR inhibitors in EGFR-mutant non-small-cell lung cancer. Oncogene 38:656–670. https://doi.org/10.1038/s41388-018-0482-y
Yonezawa T, Hasegawa S, Asai M, Ninomiya T, Sasaki T, Cha BY, Teruya T, Ozawa H, Yagasaki K, Nagai K, Woo JT (2011) Harmine, a beta-carboline alkaloid, inhibits osteoclast differentiation and bone resorption in vitro and in vivo. Eur J Pharmacol 650:511–518. https://doi.org/10.1016/j.ejphar.2010.10.048
Yu AM, Idle JR, Krausz KW, Kupfer A, Gonzalez FJ (2003) Contribution of individual cytochrome P450 isozymes to the O-demethylation of the psychotropic beta-carboline alkaloids harmaline and harmine. J Pharmacol Exp Ther 305:315–322. https://doi.org/10.1124/jpet.102.047050
Zaker F, Oody A, Arjmand A (2007) A study on the antitumoral and differentiation effects of peganum harmala derivatives in combination with ATRA on leukaemic cells. Arch Pharm Res 30:844–849. https://doi.org/10.1007/BF02978835
Zeng Y, Zhang Y, Weng Q, Hu M, Zhong G (2010) Cytotoxic and insecticidal activities of derivatives of harmine, a natural insecticidal component isolated from Peganum harmala. Molecules 15:7775–7791. https://doi.org/10.3390/molecules15117775
Zhang H, Sun K, Ding J, Xu H, Zhu L, Zhang K, Li X, Sun W (2014) Harmine induces apoptosis and inhibits tumor cell proliferation, migration and invasion through down-regulation of cyclooxygenase-2 expression in gastric cancer. Phytomedicine 21:348–355. https://doi.org/10.1016/j.phymed.2013.09.007
Zhang L, Zhang F, Zhang W, Chen L, Gao N, Men Y, Xu X, Jiang Y (2015) Harmine suppresses homologous recombination repair and inhibits proliferation of hepatoma cells. Cancer Biol Ther 16:1585–1592. https://doi.org/10.1080/15384047.2015.1078021
Zhang P, Huang CR, Wang W, Zhang XK, Chen JJ, Wang JJ, Lin C, Jiang JW (2016a) Harmine hydrochloride triggers G2 phase arrest and apoptosis in MGC-803 cells and SMMC-7721 cells by upregulating p21, activating caspase-8/bid, and downregulating ERK/Bad pathway. Phytother Res 30:31–40. https://doi.org/10.1002/ptr.5497
Zhang XF, Sun RQ, Jia YF, Chen Q, Tu RF, Li KK, Zhang XD, Du RL, Cao RH (2016b) Synthesis and mechanisms of action of novel harmine derivatives as potential antitumor agents. Sci Rep 6:33204–33219. https://doi.org/10.1038/srep33204
Zhang J, Zhang Z, Shu B, Cui G, Zhong G (2018) Cytotoxic and apoptotic activity of the novel harmine derivative ZC-14 in Sf9 cells. Int J Mol Sci 19:811–823. https://doi.org/10.3390/ijms19030811
Zhao L, Wink M (2013) The beta-carboline alkaloid harmine inhibits telomerase activity of MCF-7 cells by down-regulating hTERT mRNA expression accompanied by an accelerated senescent phenotype. Peer J 1:e174–e190. https://doi.org/10.7717/peerj.174
Zhao T, He YQ, Wang J, Ding KM, Wang CH, Wang ZT (2011) Inhibition of human cytochrome P450 enzymes 3A4 and 2D6 by beta-carboline alkaloids, harmine derivatives. Phytother Res 25:1671–1677. https://doi.org/10.1002/ptr.3458
Zhao T, Zheng SS, Zhang BF, Li YY, Bligh SW, Wang CH, Wang ZT (2012) Metabolic pathways of the psychotropic-carboline alkaloids, harmaline and harmine, by liquid chromatography/mass spectrometry and NMR spectroscopy. Food Chem 134:1096–1105. https://doi.org/10.1016/j.foodchem.2012.03.024
Zhao T, Ding KM, Zhang L, Cheng XM, Wang CH, Wang ZT (2013) Acetylcholinesterase and butyrylcholinesterase inhibitory activities of beta-carboline and quinoline alkaloids derivatives from the plants of genus peganum. J Chem 5:717232–717237. https://doi.org/10.1155/2013/717232
Zhong Z, Tao Y, Yang H (2015) Treatment with harmine ameliorates functional impairment and neuronal death following traumatic brain injury. Mol Med Rep 12:7985–7591. https://doi.org/10.3892/mmr.2015.4437
Zhu G, Zhu L, Jiang X, Zou J, Zhuang Z, Yuan W (2017) The antiviral effects of harmine against BoHV-1 infection in vitro. Lett Drug Des Discov 14:1–1. https://doi.org/10.2174/1570180814666170425155554
Acknowledgements
This work was supported by Jiangsu innovation and entrepreneurship training program for college students (202012806042H).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Zhang, L., Li, D. & Yu, S. Pharmacological effects of harmine and its derivatives: a review. Arch. Pharm. Res. 43, 1259–1275 (2020). https://doi.org/10.1007/s12272-020-01283-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-020-01283-6